Project Summary Nociception is the sensory reception and processing of noxious stimuli, which is perceived as pain in humans. Nociceptive sensitization occurs after presentation of a noxious stimulus, and in humans can result in chronic conditions such as allodynia or hyperalgesia, where normally innocuous stimuli are perceived as painful. It has been suggested that nociceptive sensitization in invertebrates may be models of allodynia or hyperalgesia, and this project aims to use the defensive strike response in the hornworm Manduca sexta as a model of allodynia and hyperalgesia. As an invertebrate, M. sexta is unregulated, has a simple nervous system that can be maintained with minimal aeration in vitro for hours to days, and has a quantifiable defensive strike in vivo. Moreover, vertebrate pain signaling molecules appear to have homologous counterparts in insects. The goals of this project are to: 1) Characterize nociceptive sensitization in M. sexta, in terms of the duration of the response and the types of stimuli inducing sensitization. 2) Identify the sensory network and nociceptors in M. sexta electrophysiologically and immunohistochemically, and 3) Verify the molecular mechanism of sensitization and analgesia.